Developing an orally active insulin from Astragalus membranaceus

Abstract

With global diabetes rates reaching epidemic levels, reliance on antidiabetic treatment will only increase. Current antidiabetic treatments lack oral delivery methods due to the peptidic nature of insulin. Digestive acids and enzymes degrade insulin before it can be absorbed into the bloodstream. Huang qi (A. Membranaceus) is listed as one of 50 fundamental herbs used in traditional Chinese medicine (TCM) and has been used in diabetic treatment. The Huang qi-derived α-astratide (aM1) is a 37 amino acid long hyper-disulfided PA1b-like peptide with three interlocking disulfide linkages granting stability against thermal, acidic and enzymatic degradation. However, very little is known about the recently discovered aM1. Here we report on the functional characterization of aM1. Toxicity studies showed that aM1 is non-toxic to cells. Cell-based glucose uptake assays showed that aM1 is an adaptogen, able to maintain cellular glucose homeostasis through increased glucose uptake in mouse muscle cell-lines. Discovery of aM1 might open a new window into developing safe orally active insulin.